PMID- 10562307
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20240408
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 10
DP  - 1999 Nov
TI  - Naturally processed and presented epitopes of the islet cell autoantigen IA-2 
      eluted from HLA-DR4.
PG  - 1449-57
AB  - During immune responses, antigen-presenting cells (APCs) process antigens and 
      present peptide epitopes complexed with human leukocyte antigen (HLA) molecules. 
      CD4 cells recognize these naturally processed and presented epitopes (NPPEs) 
      bound to HLA class II molecules. Epitope identification is important for 
      developing diagnostic and therapeutic tools for immune-mediated diseases and 
      providing insight into their etiology, but current approaches overlook effects of 
      natural processing on epitope selection. We have developed a technique to 
      identify NPPEs using mass spectrometry (MS) after antigen is targeted onto APCs 
      using a lectin-based antigen delivery system (ADS). We applied the technique to 
      identify NPPEs of the intracellular domain of the type 1 diabetes 
      mellitus-associated (type 1 DM-associated) autoantigen insulinoma-associated-2 
      (IA-2ic), presented by HLA-DR4 (0401). IA-2ic-derived NPPEs eluted from HLA-DR4 
      constitute 6 sets of peptides nested around distinct core regions. Synthetic 
      peptides based on these regions bind HLA-DR4 and elicit primary T-cell 
      proliferation frequently in HLA-DR4-positive type 1 DM patients, but rarely in 
      non-HLA-DR4 patients, and in none of the HLA-DR4 nondiabetic controls we tested. 
      This flexible, direct approach identifies an HLA allele-specific map of NPPEs for 
      any antigen, presented by any HLA class II molecule. This method should enable a 
      greater understanding of epitope selection and lead to the generation of 
      sensitive and specific reagents for detecting autoreactive T cells.
FAU - Peakman, M
AU  - Peakman M
AD  - Department of Immunology, Guy's, King's and St. Thomas' School of Medicine, 
      King's College London, Denmark Hill Campus, London SE5 9PJ, United Kingdom. 
      mark.peakman@kcl.ac.uk
FAU - Stevens, E J
AU  - Stevens EJ
FAU - Lohmann, T
AU  - Lohmann T
FAU - Narendran, P
AU  - Narendran P
FAU - Dromey, J
AU  - Dromey J
FAU - Alexander, A
AU  - Alexander A
FAU - Tomlinson, A J
AU  - Tomlinson AJ
FAU - Trucco, M
AU  - Trucco M
FAU - Gorga, J C
AU  - Gorga JC
FAU - Chicz, R M
AU  - Chicz RM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Fragments)
RN  - EC 3.1.3.48 (PTPRN protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 8)
SB  - IM
CIN - J Clin Invest. 1999 Dec;104(11):1487-9. PMID: 10587509
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Antigen-Presenting Cells/*immunology
MH  - Arthritis, Rheumatoid/genetics/*immunology
MH  - Autoantibodies/analysis
MH  - Autoantigens/*immunology
MH  - B-Lymphocytes
MH  - Cell Line
MH  - Cell Membrane/immunology
MH  - Child
MH  - Diabetes Mellitus, Type 1/genetics/*immunology
MH  - Epitopes/chemistry/*immunology/isolation & purification
MH  - Europe
MH  - Genotype
MH  - HLA-DR4 Antigen/*immunology
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Lymphocyte Activation
MH  - Membrane Proteins/chemistry/*immunology
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Peptide Fragments/chemistry/immunology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1
MH  - Protein Tyrosine Phosphatases/chemistry/*immunology
MH  - Receptor-Like Protein Tyrosine Phosphatases, Class 8
MH  - T-Lymphocytes/immunology
MH  - United States
MH  - White People
PMC - PMC409844
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
PMCR- 1999/11/15
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
PHST- 1999/11/15 00:00 [pmc-release]
AID - 07936 [pii]
AID - 10.1172/JCI7936 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Nov;104(10):1449-57. doi: 10.1172/JCI7936.